Toll样受体4拮抗剂厄立特兰对抑郁症大鼠模型前额叶和海马神经元发生和γ-氨基丁酸谷氨酸平衡的影响  

Effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in prefrontal lobe and hippocampus of depressive rats

作　　者：彭亮[1] 董汉宁[1] 余雪丹 刘忠纯 PENG Liang;DONG Han-ning;YU Xue-dan;LIU Zhong-chun(Department of Psychological Rehabilitation,Wuhan Hankou Hospital,Wuhan 430000,China)

机构地区：[1]武汉市汉口医院心理康复科

出　　处：《海南医学院学报》2019年第20期1532-1535,1541,共5页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(81271496)~~

摘　　要：目的:研究探讨Toll样受体4拮抗剂厄立特兰对抑郁症大鼠模型前额叶和海马神经元发生和γ-氨基丁酸谷氨酸平衡的影响。方法:选取100只健康的SD大鼠为本研究对象,分为健康对照组、空白对照组、厄立特兰组(低剂量组、中剂量组、高剂量组),每组大鼠各20只。建立大鼠抑郁症模型,待造模完成后,空白对照组给予生理盐水注射、厄立特兰组大鼠分别给予高、中、低剂量的厄立特兰注射液进行注射治疗。于连续给药21 d后对各组大鼠的自发活动总路程、强迫游泳不动时间、前额叶和海马神经元中的γ-氨基丁酸谷氨酸(GABA)、谷氨酸(Glu)、Toll样受体4(TLR-4)蛋白水平进行检测对比。并采用Pearson相关性检验对抑郁症大鼠的TLR4与GABA、Glu水平相关性进行分析探讨。结果:与健康对照组大鼠相比,空白对照组、厄立特兰组的自发活动总路程均显著降低,强迫游泳不动时间显著增加(P<0.05),空白对照组与厄立特兰组间比较,差异具有统计学意义(P<0.05),且厄立特兰组大鼠随着剂量的增加,自发活动总路程呈递增趋势,强迫游泳不动时间呈降低趋势(P<0.05)。与健康对照组相比,空白对照组、厄立特兰组大鼠前额叶、海马区的GABA水平有显著降低,Glu、TLR4水平显著升高,且厄立特兰组GABA高于空白对照,Glu、TLR4水平低于空白对照组,厄立特兰组内,随着剂量的增加,GABA显著升高,Glu、TLR4显著降低(P<0.05)。经Pearson相关性检验分析,TLR4与GABA呈负相关,与Glu呈正相关性(P<0.05)。结论:厄立特兰能够降低抑郁症对大鼠前额叶和海马神经元发生和γ-氨基丁酸谷氨酸平衡的影响,发挥作用的机制是厄立特兰通过拮抗Toll样受体4,进而升高GABA水平,降低Glu水平,从而发挥前额叶和海马神经元的神经保护作用。Objective:To investigate the effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in the prefrontal lobe and hippocampus of depressive rats.Methods:A total of 100 healthy SD rats were divided into healthy control group,blank control group and Eritram group(low dose group,medium dose group and high dose group),20 rats in each group.The depression model of rats in blank control group and Salvia miltiorrhiza group was established.After the completion of the model,rats in the blank control group were injected with normal saline and rats in the Eritrean group were injected with high,medium and low doses of Eritrean injection respectively.After 21 d of continuous administration,the total distance of spontaneous activity,the immobility time of forced swimming,the levels of gamma-aminobutyric glutamate(GABA),glutamate(Glu)and Toll-like receptor 4(TLR-4)protein in prefrontal lobe and hippocampal neurons were measured and compared.Pearson correlation test was used to analyze the correlation between TLR4 and GABA,Glu levels in depressive rats.Results:Compared with the healthy control group,the total spontaneous activity distance of the blank control group and Eritrean group decreased significantly,and the immobility time of forced swimming increased significantly(P<0.05).There was a significant difference between the blank control group and Eritrean group(P<0.05).The rats in Eritrean group spontaneously survived with the increase of dose.The total distance increased,while the immobility time of forced swimming decreased(P<0.05).Compared with the healthy control group,the levels of GABA in the prefrontal lobe and hippocampus of rats in blank control group and Eritrean group decreased significantly,the levels of Glu and TLR4 increased significantly,and the levels of GABA in Eritrean group were higher than those in blank control group,and the levels of Glu and TLR4 were lower than those in blank control group.TLR4 and TLR4 decreased significantly(P<0.05).Pearson corr

关 键 词：抑郁症 前额叶 海马神经元 γ-氨基丁酸谷氨酸 厄立特兰 TOLL样受体4 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]